ADENOSINE INHIBITS ALPHA-MELANOCYTE-STIMULATING HORMONE-RELEASE FROM FROG PITUITARY MELANOTROPHS - EVIDENCE FOR THE INVOLVEMENT OF A1 ADENOSINE RECEPTORS NEGATIVELY COUPLED TO ADENYLATE-CYCLASE

Adenosine is recognized as an important modulator of cell activity in particular, adenosine regulates the secretion of adrenocorticotropin from anterior pituitary cells. However, the possible role of adenosine on the pars intermedia has never been investigated. In the present study, we have examined the effect of adenosine on alpha-melanotropin (alpha-MSH) secretion from the intermediate lobe of the pituitary of the frog (Rana ridibunda), using the perifusion technique, When whole neurointermediate lobes were exposed to graded doses of adenosine (10(-9) to 10(-4) M), a dose-dependent inhibition of alpha-MSH release was observed. Repeated pulses of adenosine (5 x 10(-5) M) induced a reproducible inhibition of alpha-MSH secretion without any desensitization phenomenon. The effect of adenosine was mimicked by the non-selective agonist 5'-N-ethylcarboxamide-adenosine and the highly specific adenosine A1 receptor agonist N6-[R-phenylisopropyl]-adenosine (R-PIA). In contrast the selective adenosine A2 receptor agonist, CGS 21680, induced a slight stimulation of alpha-MSH release. Adenosine-induced inhibition of alpha-MSH secretion was blocked by the non-selective adenosine antagonist, 8-(p-sulfophenyl)-theophylline. Adenosine and R-PIA also inhibited alpha-MSH secretion from acutely dispersed pars intermedia cells. Adenosine did not block thyrotropin-releasing hormone-induced alpha-MSH release from perifused neurointermediate lobes. In contrast, adenosine inhibited both acetylcholine-evoked and muscarine-evoked alpha-MSH secretion. Finally, R-PIA induced a significant inhibition of basal and forskolin-stimulated cyclic AMP levels in whole neurointermediate lobes. The present results demonstrate that adenosine exerts a direct inhibitory effect on alpha-MSH release from melanotrope cells through activation of the A1 receptor subtype, negatively coupled to adenylate cyclase. These data suggest that adenosine may play a physiological role in the regulation of hormone release from the intermediate lobe of the pituitary.